7-21900989-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The NM_018719.5(CDCA7L):c.*1333C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,559,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: CDCA7L NM_018719.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.394

Genes affected

CDCA7L (HGNC:30777): (cell division cycle associated 7 like) Acts upstream of or within positive regulation of cell population proliferation. Located in cytosol; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-21900989-G-A is Benign according to our data. Variant chr7-21900989-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1584775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDCA7L	NM_018719.5	c.*1333C>T		3_prime_UTR_variant	10/10	ENST00000406877.8
DNAH11	NM_001277115.2	c.13304-18G>A		intron_variant		ENST00000409508.8
CDCA7L	NM_001127370.3	c.*1333C>T		3_prime_UTR_variant	11/11
CDCA7L	NM_001127371.3	c.*1333C>T		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDCA7L	ENST00000406877.8	c.*1333C>T		3_prime_UTR_variant	10/10	1	NM_018719.5	P1
DNAH11	ENST00000409508.8	c.13304-18G>A		intron_variant		5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes AF: 0.000415 AC: 63 AN: 151732 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000149 AC: 32 AN: 215322 Hom.: 0 AF XY: 0.000128 AC XY: 15 AN XY: 116748

Gnomad AFR exome AF: 0.000819

Gnomad AMR exome AF: 0.000186

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000180

Gnomad SAS exome AF: 0.0000429

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000108

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000116 AC: 164 AN: 1407974 Hom.: 0 Cov.: 33 AF XY: 0.000104 AC XY: 72 AN XY: 695392

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.000191

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000771

Gnomad4 SAS exome AF: 0.0000520

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.0000949

Gnomad4 OTH exome AF: 0.000207

GnomAD4 genome AF: 0.000415 AC: 63 AN: 151850 Hom.: 0 Cov.: 33 AF XY: 0.000471 AC XY: 35 AN XY: 74252

Gnomad4 AFR AF: 0.00117

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000256 Hom.: 0

Bravo AF: 0.000453

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 7 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Aug 21, 2023

- -

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.2
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs114694338; hg19: chr7-21940607; COSMIC: COSV100178072; COSMIC: COSV100178072;